Sergio Veiga Lopes

The Early and Midterm Function of Decellularized Aortic Valve Allografts

BACKGROUND This study evaluates the early and midterm results of decellularized aortic valve allografts (DAVA) as an aortic valve replacement. METHODS Between October 2005 and February 2010, 41 patients, 28 of whom were male, with a median age of 34 years (range, 0.1 to 71), had aortic valve replacement with DAVA. Decellularization was obtained with a 0.1% sodium dodecyl sulfate solution. Postoperative evaluation was performed with serial echocardiograms, magnetic resonance imaging, and multislice computed tomography studies to evaluate valve hemodynamics, allograft conduit dimensions, and calcification scores. RESULTS There were 3 early deaths and 1 late death, with a mean follow-up of 19 months (range, 1 to 53). There was 1 reoperation due to a failed mitral valve repair. By echocardiography in all patients, the median immediate postoperative peak gradient was 7 mm Hg (range, 1 to 26 mm Hg), and at last follow-up it was 4 mm Hg (range, 1 to 16 mm Hg); valvular regurgitation was graded as none or trivial in all but 1 patient, who had a regurgitation graded as mild to moderate. By magnetic resonance imaging (n = 4), mean root dimensions were stable at the annulus (24 mm), sinus of Valsalva (33 mm), and sinotubular junction (28 mm). By computed tomography (n = 22), there was only discrete conduit calcification (median calcium score 63 Hounsfield units [HU]; range, 0 to 894 HU) to 3 years of follow-up. Conduit biopsy in the patient who underwent reoperation demonstrated well-preserved wall structure, absence of calcification, and limited in vivo host repopulation. CONCLUSIONS The early and midterm results with DAVA demonstrated stable structural integrity, low rate of calcification, and adequate hemodynamics. Although longer periods of observation are necessary, DAVA appears to be a promising alternative for aortic valve replacement in selected patients.

Is There a Possibility for a Glutaraldehyde-Free Porcine Heart Valve to Grow?

Objective: A challenging issue is to create a heart valve with growth and remodeling potential, which would be of great interest for congenital heart valve surgery. This study was performed to evaluate the growth and remodeling potentials of a decellularized heart valve. Methods: In 4 juvenile sheep (age 12 ± 1 weeks) with a weight of 24.3 ± 4.4 kg, a 17-mm diameter decellularized porcine valve was implanted as pulmonary valve replacement. Valve growth was evaluated by transthoracic echocardiography. At explantation, valves were evaluated by gross examination, light microscopy (hematoxylin and eosin, von Kossa, Sirius red, Weigert and Gomori staining), electron microscopy and immunohistochemistry. Atomic absorption spectrometry was performed to evaluate calcium content. Results: All animals showed fast recovery. The mean follow-up was 9.0 ± 1.8 months. All sheep at least doubled their weight (54.3 ± 9.2 kg). Echocardiography showed no regurgitation and a flow velocity of 0.7 ± 0.1 m/s at the latest follow-up. The valve diameter increased from 17.6 ± 0.5 to 27.5 ± 2.1 mm (p < 0.018). Gross examination showed a similar wall thickness of the implanted valve and native pulmonary wall, with smooth and pliable leaflets. Histology showed a monolayer of endothelial cells, fibroblast ingrowth and production of new collagen. No calcification was seen at von Kossa staining, confirmed by low calcium content levels of the valve wall and leaflets at atomic absorption spectrometry. Conclusions: This glutaraldehyde-free heart valve showed not only the absence of calcification, but also remodeling and growth potential.

Long-term results of the Ross operation: An 18-year single institutional experience

OBJECTIVES The purpose of the study was to assess the 18-year outcome of the Ross operation (RO), with emphasis on survival, reoperations, and late function of the pulmonary autografts (PAs) and the right-sided pulmonary allografts. METHODS Between May 1995 to July 2013, 414 patients with a mean age (mean ± standard deviation) of 30.8 ± 13.1 years were submitted to an RO with the root replacement (n = 356) or the inclusion (n = 58) technique. The most prevalent aetiology was bicuspid valve (n = 206, 49.8%). Patients were divided in four groups depending on the type of allograft used on the right side. The mean follow-up was 8.2 ± 5.2 years and was 97.7% complete. In addition to longitudinal outcomes determined by means of the Kaplan-Meier analysis, log-rank test and Cox regression analysis were used to identify predictors of valve failure. RESULTS The early mortality rate was 2.7% and the late survival rate was 89.3% at 15 years, similar to an age- and sex-matched population. There were 22 reoperations on the PA (90.7% freedom at 15 years) and 15 on the pulmonary allografts (92.5% freedom at 15 years). The freedom rate from more than mild aortic insufficiency (AI) was 73.1% at 15 years. Thirty-three patients presented with a late root diameter >45 mm, corresponding to a freedom rate of 72.4% at 15 years. Patients with AI and a dilated annulus, especially males, are at greater risk for these complications. Among the right-sided allografts, fresh decellularized allografts showed significantly superior freedom from structural valve dysfunction. CONCLUSIONS The RO was associated with excellent long-term survival and low incidence of reoperations up to 15 years. Male patients with AI and dilated annulus are at increased risk for late insufficiency and root dilatation. Fresh decellularized allografts presented the best results for reconstruction of the right ventricular outflow tract.

Results of a decellularized porcine heart valve implanted into the juvenile sheep model.

OBJECTIVE This study was performed to evaluate the possibility of creating a glutaraldehyde-free porcine xenograft to improve long-term durability. METHODS A decellularized porcine pulmonary valve was implanted into the right ventricular outflow tract of 7 juvenile sheep. Valves were explanted after 3 months (n = 4) and 6 months (n = 3). Evaluation was performed by gross examination, radiography, histology (hematoxylin-eosin and Sirius red staining), and immunohistochemistry. Quantitative determination of calcium content was investigated by atomic absorption spectrometry. RESULTS All animals showed fast recovery without complications. At explantation, all decellularized valves showed smooth and pliable leaflets without evidence of thrombosis. The valve wall was also smooth and pliable without hardness. Light microscopy showed a monolayer of host endothelial cells covering the inner surface of the heart valves and repopulation of host fibroblasts into the deeper layers. Sirius red staining enabled visualization of the production of new collagen. Radiographic results showed an absence of calcification, confirmed by the low calcium levels (1.08 +/- 0.28 microg/g and 0.73 +/- 0.31 microg/g at 3 and 6 months, respectively) revealed by atomic absorption spectrometry. CONCLUSIONS The results with the juvenile sheep model showed that decellularized heart valves are recellularized in vivo. Host endothelial cells form a monolayer on the inner surface of the valve matrix. Furthermore, host fibroblasts repopulate the valve matrix and produce collagen; thus, a remodeling potential can be expected.

Operação de Ross com homoenxertos valvares decelularizados: resultados de médio prazo

Objective: To evaluate the medium-term results (4 years) of decelularized allografts during Ross Operation. Method: From January 2003 to February 2007, 68 patients underwent Ross Operation with decelularized allografts. Forty eight were male and the mean age was 30.3±11.2 years. Decelularization was done with deoxicolic acid (DOA) in 35 cases and with sodium dodecylsulfate (SDS) in 33. For comparison of the gradients, 68 patients with cryopreserved allografts and matched for age were selected. All patients had a control echo before hospital discharge and annually thereafter. In addition, eight patients had MRI studies. In two patients, samples of the conduit wall were analyzed by histological analysis. Results: There was one (1.4%) early death. In the late follow-up, there were two reoperations for endocarditis and one late death. The early gradients varied between 4 - 29 mmHg (m= 10.3± 5.5mmHg) and exhibited an increase to 16.5±12.2 mmHg (min= 4, max= 45) at 24 months postoperatively. There were no significant differences when compared to the cryopreserved group. There was, however, a tendency towards lesser gradients in the SDS decelularized group after 12 months. Histological analysis revealed partial reendothelization and progressive repopulation of the tunica media media wall with autogenous cells. There was no progressive pulmonary insufficiency. The MRI results showed a lesser tendency to shrinkage in the decelularized conduits.

Decellularized heterografts versus cryopreserved homografts: experimental study in sheep model

OBJECTIVES The aim of this study is to assess the biological behaviour of porcine decellularized heterografts (Desc group) compared with cryopreserved homografts (Crio group) implanted in juvenile sheep. METHODS Decellularized porcine pulmonary heterografts were implanted in five animals and cryopreserved pulmonary homografts in another five. The animals were followed-up for a mean of 280 +/- 14 days. The valve diameter was measured by echocardiography, which was performed at the 30th postoperative day, and before the explantation. The valves were also assessed macroscopically. Histological evaluation was performed using H.E., Gomori and Weigert staining. Immunohistochemistry specified different cell types (Factor VIII, CD3, Vimentin and CD68). Calcium quantity was analyzed using atomic absortion spectometry. RESULTS There was one death in the Desc group due to endocarditis. The valves of Crio group showed decrease in the cellularity whereas the valves of Desc group showed matrix repopulation with endothelial and interstitial cells. Loss of collagen density and disarrangement of the normal fiber architecture was observed in Crio group. Calcium content demonstrated higher levels on the cusps and conduits in Crio group comparatively with Desc group. (P=0.016). The mean valvular diameter at the explantation was significantly increased (P=0.025) in the Desc group. CONCLUSIONS Decellularized heterografts had a different biological behaviour when compared to cryopreserved homografts and become repopulated by cells with fibroblasts and endothelial cells characteristics. The matrix was preserved and some regenerative potential was present.

Dez anos de experiência com a operação de Ross

OBJECTIVE To evaluate the 10-year outcomes of the Ross Operation, analyzing survival rate, incidence of reoperations, and late performance of pulmonary autografts and homografts in the reconstruction of the right ventricular outflow tract. METHODS Two hundred and twenty seven patients with a mean age of 29.1 +/- 11 years underwent Ross operation from May 1995 to February 2005. The most prevalent etiology was rheumatic disease in 61% of the cases. Autografts were implanted using the total root replacement technique in 202 cases, with intraluminal cylinder in 20, and in the subcoronary position in 5. The right ventricular outflow tract was conventionally reconstructed with cryopreserved homografts (n = 160), with proximal extension of the homograft with pericardium (n = 41), and with decellularized homografts (n = 26). The postoperative follow-up ranged from 1 to 118 months (mean = 45.5 months). RESULTS Hospital mortality was 3.5%, and long-term survival was 96.9% at ten years. No episodes of thromboembolism and only two cases of endocarditis occurred. Eleven patients underwent reoperation because of problems related to the auto and/or homograft, progression of rheumatic mitral valve disease, and iatrogenic coronary insufficiency. After 10 years, 96.4% and 96.2% of the patients were free from reoperation in the autograft and homograft groups, respectively. No late autograft dilatation was observed. Reconstruction of the left ventricular outflow tract with decellularized homografts significantly reduced the incidence of gradients on late follow-up. CONCLUSION Late outcomes with the Ross Operation were associated with an excellent long-term survival and a low incidence of reoperations and late morbidity. We consider this procedure the best option for the surgical treatment of aortic valve disease in children and young adults.

Aortic valve replacement with the Cardioprotese Premium bovine pericardium bioprosthesis: four-year clinical results

OBJECTIVES This study reports the initial clinical and echocardiographic results of the Premium bioprosthetic aortic valve up to 4 years of follow-up. METHODS Between October 2007 and July 2011, 121 consecutive patients were submitted for aortic valve replacement with the Premium bioprosthetic valve. The mean age was 68 ± 9 years and 64 patients were males. The patients were periodically evaluated by clinical and echocardiographic examinations. The mean follow-up was 21 months (min = 2, max = 48), yielding 217 patients/year for the analysis. RESULTS The hospital mortality was 8%. Late survival at 3 years was 89% (95% CI: 81.9-93.3%), and 80% of the patients were in NYHA functional class I/II. The rates of valve-related complications were low, with a linearized incidence of 0.9%/100 patients/year for thromboembolic complications, 0% for haemorrhagic events and 0.9%/100 patients/year of bacterial endocarditis. There was no case of primary structural valve dysfunction. The mean effective orifice area was 1.61 ± 0.45 cm(2); mean gradient 13 ± 5 mmHg and peak gradient 22 ± 9 mmHg. Significant patient-prosthesis mismatch was found in only 11% of the cases. CONCLUSIONS The Premium bioprosthetic aortic valve demonstrated very satisfactory clinical and echocardiographic results up to 4 years, similar to other commercially available, third-generation bioprosthetic valves.

Experimental study with deccelularized porcine heterografts: the prosthesis of the future

OBJETIVO: Avaliar, comparativamente, o comportamento de homoenxertos valvares criopreservados e de heteroenxertos descelularizados implantados na via de saida do ventriculo direito de carneiros jovens, assim como relatar a experiencia clinica inicial com homoenxertos descelularizados em pacientes submetidos a operacao de Ross. METODO: No grupo A, foram implantados quatro homoenxertos pulmonares criopreservados e no Grupo B, quatro heteroenxertos porcinos valvares descelularizados com acido deoxicolico. Em cada grupo, dois animais foram sacrificados no 3o mes e dois no 5o mes de pos-operatorio. As pecas foram avaliadas macroscopicamente e por radiografias, alem de exame microscopico com coloracoes HE, Tricromico de Mallory e Sirius Red. A experiencia clinica com quatro pacientes submetidos a operacao de Ross com emprego de homoenxertos valvares descelularizados e relatada. RESULTADOS: Todos os animais sobreviveram. Os ecocardiogramas demonstraram boa funcao valvar nos dois grupos. Embora as cuspides valvares em ambos os grupos tivessem aspecto macroscopico normal, a mensuracao de calcio e o estudo radiologico demonstraram inicio de calcificacao focal nos homoenxertos criopreservados, mas nao nos heteroenxertos descelularizados. Esses achados foram confirmados por exames microscopicos. Os homoenxertos criopreservados demonstraram perda de sua celularidade, enquanto que os heteroenxertos descelularizados demonstraram repopulacao progressiva da matriz colagena com fibroblastos, assim como reendotelizacao. Os quatro pacientes operados tiveram evolucao pos-operatoria imediata satisfatoria, com funcao normal dos homoenxertos. CONCLUSOES: Heteroenxertos valvares descelularizados foram progressivamente repopulados por celulas autogenas e exibiram minima tendencia a calcificacao no modelo estudado. Esses resultados sugerem que homoenxertos descelularizados possam ter alguma capacidade regenerativa e com isso ter durabilidade superior aos homoenxertos criopreservados convencionais.

An Experimental Study of Decellularized Xenografts Implanted Into the Aortic Position with 4 Months of Follow Up

This study evaluated decellularized stentless porcine xenografts into the aortic position of seven juvenile sheep. The hemodynamic performance were analyzed by means of echocardiographic examination. Post mortum, specimens were evaluated by gross examination, light microscopy, and immunohistochemical staining. Explantations were performed at up to four months. Echocardiographic evaluation examination showed a maximum flow velocity of 0.94m/s with absence of regurgitation. Gross examination showed smooth and pliable leaflets endothelial cells covered the valve wall and leaflets, deeper layers presented ingrowth of host interstitial cells. There was no evidence for calcification. Our preliminary results showed excellent hemodynamics. Regeneration by host cells and absence of calcifications was observed at 4 months follow-up within the systemic circulation.